A comparison of effect of insulin on hepatic metabolites, gluconeogenesis, and ketogenesis

In 12-h fasted rats given tryptophan, insulin decreased the hepatic content of alanine and the three precursors of oxalacetate-malate, citrate, and aspartate-while elevating hepatic pyruvate. These changes are consistent with suppression of the pyruvate carboxylase step. Animals fasted for 24 h lose the effect on oxalacetate precursors, and this correlates with a loss of suppression of hepatic ketones. The decrease in hepatic alanine and oxalacetate precursors is more sensitive than the blood sugar. However, the conversion of labeled lactate to glucose is not inhibited by insulin in 12-h fasted animals. (+)-Decanoylcarnitine also produces a decrease in oxalacetate precursors comparable to insulin and a lowering of the blood sugar. However, in fasted animals not given tryptophan it does not alter the blood sugar. Therefore, in tryptophan-treated animals alterations of fatty acid oxidation by insulin or (+)-decanoylcarnitine produce a fall in oxalacetate precursors consistent with inhibition of pyruvate carboxylase but this does not equate with overall suppression of gluconeogenesis by either of these agents in the absence of tryptophan.